Preparation And Characterization Of Lenalidomide-Nicotinamide Cocrystal

Pharmaceutical cocrystal is a new type of drug solid form, differing from the solvate and hydrate etc. It can improve the molecular’s physical and chemical properties without changing the structure of the active ingredient, such as solubility, stability and bioavailability. Pharmaceutical cocrystal has become the focus in the crystal engineering.The work looks lenalidomide and nicotinamide as the research object, studying the preparation methods, characterization and solubility.Lenalidomide-nicotinamide cocrystal was prepared by different methods, including solvent drop grinding, dry grinding and slurry crystallization. The products were identified by powder X-ray diffraction, differential scanning calorimetry, thermo-gravimetric and infrared spectroscopy analysis. After establishing the qualitative analysis of the cocrystal, the effects of grinding time, solvent type on the process of preparing the cocrystal were studiedThe solubilities of lenalidomide, nicotinamide and their cocrystal were determined by using the static method in the water, methanol and ethanol. The results were correlated by apelblat simplified emirical equation and ?h equation, and the correlation datum matched with experimental datum,which showed a fine fit to the experimental data.DFT B3LYP/6-31G(d)was also used to calculate the binding energy of the cocrystal, and simulate the effect of solvent in the solubility. It provides a method to screen the CCF and solvents.The transformation rate of solid state in prepararing cocrystal was determined by DSC.